CoChat
Sign Up
Cited by 56Iron Metabolism and DisordersClinical Laboratory Practices and Quality ControlHematological disorders and diagnostics

Sex, lies, and iron deficiency: a call to change ferritin reference ranges

Open access
Martens, Kylee, DeLoughery, Thomas G.·2023·Hematology
DOI 10.1182/hematology.2023000494PMC PMC10727104
Open this paper in CoChat — free accountOpen PDF

Abstract

Iron deficiency is a very common and treatable disorder. Of all the tests available to diagnose iron deficiency, the serum ferritin is the most able to discriminate iron deficiency from other disorders. However, the reference range for ferritin in many laboratories will lead to underdiagnosis of iron deficiency in women. Studies have shown that 30%-50% of healthy women will have no marrow iron stores, so basing ferritin cutoffs on the lowest 2.5% of sampled ferritins is not appropriate. In addition, several lines of evidence suggest the body physiologic ferritin “cutoff” is 50 ng/mL. Work is needed to establish more realistic ferritin ranges to avoid underdiagnosing a readily treatable disorder.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/hematology.2023000494

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Serum ferritin is a noninvasive measure of iron stores and is the most commonly utilized biomarker for evaluating iron deficiency.

    “SF is a noninvasive measure of iron stores and is the most commonly utilized biomarker for evaluating ID [1,2,7,8,9].”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [7]

    The section “Why do we use ferritin as a measure of iron stores?” (pp. 618–619) says serum ferritin correlates with total body iron stores and describes it as the best-performing test for iron deficiency. It does not establish that ferritin is the most commonly utilized biomarker or characterize the test as noninvasive; best-performing is not the same as most-used. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • When serum ferritin is <15 ng/mL, iron levels are no longer observed in bone marrow macrophages, and most patients are already anemic.

    “When SF is <15 ng/mL, iron levels are no longer observed in bone marrow macrophages, and most patients are already anemic.”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [7]

    The sections on low iron stores in women and ferritin reference ranges report absent marrow iron in some women, supporting the general link between depleted iron stores and marrow findings. They do not establish that macrophage iron disappears below 15 ng/mL or that most patients below that level are anemic. The clinical case describes a patient with ferritin of 10 ng/mL and normal hemoglobin, though one case cannot establish the proportion who are anemic. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Serum ferritin <15 ng/mL is a reliable indicator of absolute iron deficiency, irrespective of the presence or absence of inflammatory conditions.

    “SF <15 ng/mL is a reliable indicator of absolute ID, irrespective of the presence or absence of inflammatory conditions [6,7,8,9,10].”

    From Defining Global Thresholds for Serum Ferritin: A Challenging Mission in Establishing the Iron Deficiency Diagnosis in This Era of Striving for Health Equity (2025) · cites this paper as [7]

    In “Why do we use ferritin as a measure of iron stores?” (page not specified), the paper calls ferritin a strong diagnostic test and explains that iron deficiency blunts its rise during inflammation. It does not establish the specific <15 ng/mL cutoff as reliable regardless of inflammatory status; it says the appropriate lower limit depends on the clinical scenario. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 22

  1. [3]3. Eisenstein RS, Blemings KP. Iron reg u la tory pro teins, iron respon sive ele ments and iron homeo sta sis. J Nutr. 1998;128(12):22952298.
  2. [4]4. Gelaw Y, Woldu B, Melku M. The role of retic u lo cyte hemo glo bin con tent for diag no sis of iron defi ciency and iron defi ciency ane mia, and mon i tor ing of iron ther apy: a lit er a ture review. Clin Lab. 2019;65(12).
  3. [5]5. Walters GO, Miller FM, Worwood M. Serum fer ri tin con cen tra tion and iron stores in nor mal sub jects. J Clin Pathol. 1973;26(10):770772.
  4. [6]6. Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diag no sis of irondefi ciency ane mia: an over view. J Gen Intern Med. 1992;7(2): 145153.
  5. [7]7. Harms K, Kaiser T. Beyond sol u ble trans fer rin recep tor: old chal lenges and new hori zons. Best Pract Res Clin Endocrinol Metab. 2015;29(5):799810.
  6. [8]8. Mast AE, Blinder MA, Gronowski AM, Chumley C, Scott MG. Clinical util ity of the sol u ble trans fer rin recep tor and com par i son with serum fer ri tin in sev eral pop u la tions. Clin Chem. 1998;44(1):4551.
  7. [9]9. Beutler E, Larsh SE, Gurney CW. Iron ther apy in chron i cally fatigued, nonanemic women: a dou bleblind study. Ann Intern Med. 1960;52:378394.
  8. [10]10. Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of iron sup ple men ta tion on fatigue in nonanemic men stru at ing women with low fer ri tin: a ran dom ized con trolled trial. CMAJ. 2012;184(11):12471254.
  9. [11]11. Verdon F, Burnand B, Stubi CL, et al. Iron sup ple men ta tion for unex plained fatigue in nonanae mic women: dou ble blind randomised pla cebo con trolled trial. BMJ. 2003;326(7399):1124.
  10. [12]12. Burden RJ, Morton K, Richards T, Whyte GP, Pedlar CR. Is iron treat ment ben e fi cial in irondefi cient but nonanae mic (IDNA) endur ance ath letes? A sys tem atic review and metaanal y sis. Br J Sports Med. 2015;49(21):13891397.
  11. [13]13. Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cog ni tive effects of iron sup ple men ta tion in nonanae mic irondefi cient ado les cent girls. Lancet. 1996;348(9033):992996.
  12. [14]14. Zhu XY, Wu TT, Wang HM, et al. Correlates of nonanemic iron defi ciency in rest less legs syn drome. Front Neurol. 2020;11:298.
  13. [15]15. Robach P, Recalcati S, Girelli D, et al. Alterations of sys temic and mus cle iron metab o lism in human sub jects treated with lowdose recom bi nant eryth ro poi e tin. Blood. 2009;113(26):67076715.
  14. [17]17. Scott DE, Pritchard JA. Iron defi ciency in healthy young col lege women. JAMA. 1967;199(12):897900. PMID: 6071557.
  15. [18]18. Puolakka J. Serum fer ri tin in the eval u a tion of iron sta tus in young healthy women. Acta Obstet Gynecol Scand Suppl. 1980;95:3541.
  16. [19]19. Hallberg L, Bengtsson C, Lapidus L, Lindstedt G, Lundberg PA, Hultén L. Screening for iron defi ciency: an anal y sis based on bonemar row exam i na tions and serum fer ri tin deter mi na tions in a pop u la tion sam ple of women. Br J Haematol. 1993;85(4):787798.
  17. [20]20. Rushton DH, Barth JH. What is the evi dence for gen der dif fer ences in fer ri tin and haemoglobin? Crit Rev Oncol Hematol. 2010;73(1):19.
  18. [21]21. Galetti V, Stoffel NU, Sieber C, Zeder C, Moretti D, Zimmermann MB. Threshold fer ri tin and hepcidin con cen tra tions indi cat ing early iron defi ciency in young women based on upregulation of iron absorp tion. E Clin Med. 2021;39:101052.
  19. [23]23. NilssonEhle H, Jagenburg R, Landahl S, Svanborg A. Blood haemoglobin declines in the elderly: impli ca tions for ref er ence inter vals from age 70 to 88. Eur J Haematol. 2000;65(5):297305.
  20. [24]24. Widdowson EM, McCance RA. Iron in human nutri tion. J Hyg (Lond). 1936;36(1):1323.
  21. [25]25. Natvig H, Vellar OD. Studies on hemo glo bin val ues in Norway. 8. Hemo globin, hemat o crit and MCHC val ues in adult men and women. Acta Med Scand. 1967;182(2):193205.
  22. [26]26. Merz LE, Siad FM, Creary M, Sholzberg M, Weyand AC. Laboratorybased ineq uity in throm bo sis and hemo sta sis: review of the evi dence. Res Pract Thromb Haemost. 2023;7(2):100117.

Cited by

Sorted by citations

Related

Authors
Martens, K., & DeLoughery, T. G.
Affiliations
Oregon Health & Science University (US)
Corresponding author
DeLoughery, Thomas G.
ORCID
Venue
Hematology
Publisher
American Society of Hematology
Published
2023-12-08
Volume
2023
Issue
1
Pages
617-621
ISSN
  • 1520-4383 (ISSN-L)
  • 1520-4391
DOI
10.1182/hematology.2023000494
PMC
PMC10727104
OpenAlex
W4389489502
Cited by
56
References
26
Citations by year
2026: 27 · 2025: 22 · 2024: 7
FWCI
11.52
Type
journal article
Language
en
Open access
Locations
  • Hematology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Emergency Medicine › Hematological disorders and diagnostics
Keywords
iron deficiency, serum ferritin, underdiagnosis, women, iron stores, sex differences
MeSH terms
Iron Deficiencies, Bone Marrow, Female, Ferritins, Humans, Iron, Reference Values, Anemia, Iron-Deficiency

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review